1-156880037-G-T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_002529.4(NTRK1):c.2085G>T(p.Pro695Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P695P) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
NTRK1
NM_002529.4 synonymous
NM_002529.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -5.36
Publications
0 publications found
Genes affected
NTRK1 (HGNC:8031): (neurotrophic receptor tyrosine kinase 1) This gene encodes a member of the neurotrophic tyrosine kinase receptor (NTKR) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. The presence of this kinase leads to cell differentiation and may play a role in specifying sensory neuron subtypes. Mutations in this gene have been associated with congenital insensitivity to pain, anhidrosis, self-mutilating behavior, cognitive disability and cancer. Alternate transcriptional splice variants of this gene have been found, but only three have been characterized to date. [provided by RefSeq, Jul 2008]
NTRK1 Gene-Disease associations (from GenCC):
- hereditary sensory and autonomic neuropathy type 4Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
- familial medullary thyroid carcinomaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 1-156880037-G-T is Benign according to our data. Variant chr1-156880037-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1528895.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-5.36 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_002529.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NTRK1 | NM_002529.4 | MANE Select | c.2085G>T | p.Pro695Pro | synonymous | Exon 16 of 17 | NP_002520.2 | ||
| NTRK1 | NM_001012331.2 | c.2067G>T | p.Pro689Pro | synonymous | Exon 15 of 16 | NP_001012331.1 | |||
| NTRK1 | NM_001007792.1 | c.1977G>T | p.Pro659Pro | synonymous | Exon 16 of 17 | NP_001007793.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NTRK1 | ENST00000524377.7 | TSL:1 MANE Select | c.2085G>T | p.Pro695Pro | synonymous | Exon 16 of 17 | ENSP00000431418.1 | ||
| NTRK1 | ENST00000368196.7 | TSL:1 | c.2067G>T | p.Pro689Pro | synonymous | Exon 15 of 16 | ENSP00000357179.3 | ||
| NTRK1 | ENST00000358660.3 | TSL:2 | c.2076G>T | p.Pro692Pro | synonymous | Exon 15 of 16 | ENSP00000351486.3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461354Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 726986 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461354
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
726986
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33478
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86254
European-Finnish (FIN)
AF:
AC:
0
AN:
52900
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1112000
Other (OTH)
AF:
AC:
0
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
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55-60
60-65
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70-75
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
ClinVar submissions as Germline
Significance:Likely benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
Hereditary insensitivity to pain with anhidrosis (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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